Diagnosis and management of migraine in ten steps

DOI: https://doi.org/10.1038/s41582- 021- 00509- 5

Abstract-Summary Migraine is a disabling primary headache disorder that directly affects more than one billion people worldwide.

To support clinical decision-making, we convened a European panel of experts

to develop a ten-step approach to the diagnosis and management of migraine.

Each step was established by expert consensus and supported by a review of cur- rent literature, and the Consensus Statement is endorsed by the European Headache Federation and the European Academy of Neurology.

In this Consensus Statement, we introduce typical clinical features, diagnostic

criteria and differential diagnoses of migraine.

Further, we outline best practices for acute and preventive treatment of migraine in various patient populations, including adults, children and adolescents, pregnant and breastfeeding women, and older people.

Extended: Migraine is a highly disabling primary headache disorder with a

1-year prevalence of ~15% in the general population [165, 166].

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Migraine is a ubiquitous neurological disorder that adds substantially to the

global burden of disease.

Introduction Migraine is a highly disabling primary headache disorder with a 1-year prevalence of ~15% in the general population [165, 166].

Migraine manifests clinically as recurrent attacks of headache with a range of

accompanying symptoms [16].

In approximately one third of individuals with migraine, headache is sometimes or always preceded or accompanied by transient neurological disturbances, referred to as migraine aura [167, 168].

Despite these treatment options and the comprehensive diagnostic criteria, clini- cal care remains suboptimal—misdiagnosis and under-treatment of migraine are substantial public health challenges [84, 169].

Population-based data from Europe indicate that preventive medication for migraine is used by only 2–14% of eligible individuals [84], an alarming finding that calls for global action [169].

Methods The Danish Headache Society and its representatives (A.K.E., H.A., H.W.S. and M.Ashina) conceived a European Consensus Statement on the diagnosis and clini- cal management of migraine.

A formal proposal, including a suggested list of authors, was prepared and sub- mitted to the Board of Directors of the EHF, the Chairs of the EAN Headache Panel and the Chair of the EAN Scientific Committee.

Three authors (H.A., T.J.S. and M.Ashina) identified the ten most important

steps in diagnosis and management of migraine through email correspondence.

Once these steps were agreed, seven authors (A.K.E., H.A., S.K., H.-C.D.,

H.W.S., T.J.S. and M.Ashina) wrote the initial draft.

In continuous email correspondence, all authors reviewed the initial draft and

contributed to all subsequent drafts.

Step 1: When to Suspect Migraine Migraine without aura is characterized by recurrent headache attacks that last 4–72 h [16].

Approximately one third of individuals with migraine experience aura [167],

either with every attack or with some attacks.

Aura is defined as transient focal neurological symptoms that usually precede,

but sometimes accompany, the headache phase of a migraine attack [16].

Less common aura symptoms include aphasic speech disturbance, brainstem symptoms (such as dysarthria and vertigo), motor weakness (in hemiplegic migraine) and retinal symptoms (for example, repeated monocular visual distur- bances) [16].

Many individuals with migraine with aura also experience attacks that are not

preceded by aura [16].

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3 Diagnosis

Suspect migraine without aura in a person with recurrent moderate to severe headache, particularly if pain is unilateral and/or pulsating, and when the person has accompanying symptoms such as photophobia, phonophobia, nausea and/or vomiting.

Suspect migraine with aura in a person with the symptoms above and recurrent,

short-lasting visual and/or hemisensory disturbances.

Step 2: Diagnosis of Migraine An adequate medical history must include at least the following: age at onset of headache; duration of headache episodes; frequency of headache episodes; pain characteristics (for example, location, quality, severity, aggravating factors and relieving factors); accompanying symptoms (for example, photophobia, phonopho- bia, nausea and vomiting); aura symptoms (if any); and history of acute and preven- tive medication use.

Headache (migraine-like or tension-type-like) on ≥15 days/month for >3 months

that fulfil criteria 2 and 3 2.

After use of such screening instruments, diagnosis should be confirmed by a

review of the medical history and/or use of a diagnostic headache diary.

The ID-Migraine questionnaire has a sensitivity of 0.81, a specificity of 0.75 and a positive predictive value of 0.93 when compared with ICHD-based diagnosis by a headache specialist [170].

Migraine Screen Questionnaire The Migraine Screen Questionnaire (MS-Q), like ID-Migraine, is designed to screen patients for migraine but includes five ques- tions regarding headache frequency, intensity and length, headache associated nau- sea, photophobia and phonophobia, and disability [171].

Step 3: Education and Patient Centricity Patient centricity and education have important roles in the management of migraine. Patient satisfaction is a key management outcome and treatment success depends on it but most people with migraine report at least one perceived unmet treatment need [172].

Unrealistic expectations constitute a major obstacle to achieving patient satisfac- tion — a common misconception among patients is that effective treatment means cure of their migraine [173, 174].

Education is the solution—clinicians must explain to the patient both the disease and the principles of managing it effectively, including instruction on the correct use of medication, potential adverse effects and what to do about them, and the impor- tance of avoiding medication overuse.

Contrary to popular belief, predisposing and trigger factors are of limited impor-

tance in migraine, and their role is often overemphasized [175].

Provide every patient with a full explanation of migraine as a disease and of the

principles of its management.

Step 4: Acute Treatment Those with proven efficacy include non-steroidal anti-inflammatory drugs (NSAIDs), and the strongest evidence supports use of acetylsalicylic acid, ibupro- fen and diclofenac potassium as first-line medications [176–178].

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No evidence supports the use of triptans during the aura phase of a migraine attack. When all other triptans have failed or in patients who rapidly reach peak head- ache intensity or cannot take oral triptans because of vomiting, sumatriptan by sub- cutaneous injection can be useful [179].

Upon relapse, patients can repeat their triptan treatment or combine the triptan with simultaneous intake of fast-acting formulations of naproxen sodium, ibuprofen lysine or diclofenac potassium [180, 181].

For patients who experience nausea and/or vomiting during migraine attacks, prokinetic antiemetics such as domperidone and metoclopramide are useful oral adjuncts.

Advise use of acute medications early in the headache phase of the attack, as

effectiveness depends on timely use with the correct dose.

Advise patients that frequent, repeated use of acute medication risks develop-

ment of MOH.

Step 5: Preventive Treatment Patients who are considered for preventive treatment remain adversely affected on at least 2 days per month [173], although this should not be regarded as an absolute rule [173].

For most preventive medications, clinical experience suggests that pausing can

be considered when treatment has been successful for 6–12 months [173].

The purpose of pausing is to ascertain whether preventive treatment can be stopped, which minimizes the risk of unnecessary drug exposure and allows some patients to manage their migraine with acute medications only.

A range of non-pharmacological preventive therapies can be used either as adjuncts to acute and preventive medications or instead of them if medication use is contraindicated.

Consider preventive treatment in patients who are adversely affected by migraine

on ≥2 days per month despite optimized acute treatment.

Consider neuromodulatory devices, biobehavioural therapy and acupuncture as adjuncts to acute and preventive medication or as stand-alone preventive treatment when medication is contraindicated.

Step 6: Managing Migraine in Special Populations Clinicians are advised to regularly monitor blood pressure in older patients with migraine who use triptans, in addition to periodical assessment of cardiovascular risk factors [182].

For adolescents aged 12–17 years, multiple NSAIDs and triptans have been approved for acute treatment of migraine [183, 184], and some evidence indicates that nasal spray formulations of sumatriptan and zolmitriptan are the most effec- tive [185].

Despite relatively poor efficacy, paracetamol should be used as the first-line medication for acute treatment of migraine in pregnancy [186]; NSAIDs can be used only during the second trimester [187, 188].

Preventive migraine medications are best avoided during pregnancy owing to the

potential for fetal harm.

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If preventive therapy is considered clinically indicated because of frequent and disabling migraine attacks, the best available safety data support the use of pro- pranolol or, if propranolol is contraindicated, amitriptyline.

In children and adolescents with migraine, bed rest alone might suffice; if not, use ibuprofen for acute treatment and propranolol, amitriptyline or topiramate for prevention.

In women with menstrual migraine, consider perimenstrual preventive therapy

with a long-acting NSAID or triptan.

Step 7: Follow-Up, Treatment Response and Failure Evaluation of treatment responses should include a review of effectiveness, adverse events and adherence.

HURT questionnaire The Headache Under-Response to Treatment (HURT) questionnaire is an eight-item, self-administered questionnaire developed specifi- cally to guide follow-up in primary care [189].

The questionnaire assesses treatment outcome in several domains, and responses

are coupled to suggested changes in management.

mTOQ-4 The Migraine Treatment Optimization Questionnaire (mTOQ-4) is a self-administered questionnaire that can be used to assess acute treatment, including treatment efficacy [190].

This questionnaire has been validated for use in primary care and used in several

studies to assess treatment outcomes [190–192].

If all treatments fail, the diagnosis should be questioned and specialist referral is

indicated [173].

Evaluate the effectiveness of treatment by assessing attack frequency, attack

severity and migraine-related disability.

When outcomes are suboptimal, review the diagnosis, treatment strategy, dosing

and adherence.

If all treatment fails, question the diagnosis and consider specialist referral.

Step 8: Managing Complications Some estimates suggest that up to 3% of patients with episodic migraine experience transformation to chronic migraine each year [151].

If MOH, which frequently causes symptoms that suggest chronic migraine, can

be ruled out, then a preventive treatment should be established [193].

Preventive medications for which evidence supports effectiveness in chronic migraine include topiramate [194], onabotulinumtoxinA [195] and CGRP mono- clonal antibodies [196].

Regulatory restrictions generally limit the use of onabotulinumtoxinA and CGRP antibodies to patients in whom two or three other preventive medications have failed, despite the fact that topiramate is the only other treatment with evidence sup- porting its use.

Educate patients with migraine about the risk of MOH with frequent overuse of

acute medication.

Manage established MOH by explanation and withdrawal of the overused medi-

cation; abrupt withdrawal is preferred, except for opioids.

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Once MOH is ruled out, initiate preventive medication therapy for chronic migraine; evidence-based treatment options are topiramate, onabotulinumtoxinA and CGRP monoclonal antibodies.

Step 9: Recognizing and Managing Comorbidities Migraine is associated with anxiety, depression, sleep disturbances and chronic pain conditions (for example, neck and lower back pain) [197–201].

These associations are more pronounced in people with chronic migraine than in

those with episodic migraine [202].

Recognition of comorbid conditions in migraine is important because they can

influence drug choice.

Recognition of comorbidities is also important because their alleviation can

improve treatment outcomes for migraine, and vice versa.

Ensure that comorbidities are identified in patients with migraine, as they can

affect treatment choice and outcomes.

Step 10: Long-Term Follow-Up Timely return to primary care can be made once the patient experiences sustained efficacy with preventive therapy for up to 6 months with no substantial treatment- related adverse effects.

Primary care should be responsible for the long-term management of patients

with migraine, maintaining stability and reacting to change.

Referral from specialist back to primary care should be timely and accompanied

by a comprehensive treatment plan.

The patient can be referred back to primary care once sustained efficacy with preventive therapy for up to 6  months is obtained with no substantial treatment- related adverse effects.

Conclusions Migraine is a ubiquitous neurological disorder that adds substantially to the global burden of disease.

Despite the existence of comprehensive diagnostic criteria and a multitude of therapeutic options, diagnosis and clinical management of migraine remain subop- timal worldwide.

This Consensus Statement was developed by experts from Europe to provide generally applicable recommendations for the diagnosis and management of migraine and to promote best clinical practices.

Acknowledgement A machine generated summary based on the work of Eigenbrodt, Anna K.; Ashina, Håkan; Khan, Sabrina; Diener, Hans-Christoph; Mitsikostas, Dimos D.; Sinclair, Alexandra J.; Pozo-Rosich, Patricia; Martelletti, Paolo; Ducros, Anne; Lantéri- Minet, Michel; Braschinsky, Mark; del Rio, Margarita Sanchez; Daniel, Oved; Özge, Aynur; Mammadbayli, Ayten; Arons, Mihails; Skorobogatykh, Kirill; Romanenko, Vladimir; Terwindt, Gisela M.; Paemeleire, Koen; Sacco, Simona; Reuter, Uwe; Lampl, Christian; Schytz, Henrik W.; Katsarava, Zaza; Steiner, Timothy J.; Ashina, Messoud. 2021 in Nature Reviews Neurology.

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Reference programme: diagnosis and treatment of headache disorders and facial pain. Danish Headache Society, 3rd edition, 2020